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LOCO 2 > Treatment of rheumatoid athritis > Flashcards

Treatment of rheumatoid athritis Flashcards

1
Q

As well as the joints, what does RA affect

A

Tendon sheaths

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2
Q

Is it symmetrical or asymmetrical

A

Symmetrical

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3
Q

What criteria is used to diagnose rheumatoid athritis

A

ACR/EULAR criteria

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4
Q

3 types of drugs used to manage rheumatoid athritis

A
  • Pain relief drugs
  • Drugs to modify disease progression
  • Adjunct therapy
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5
Q

What drug type can be used to manage rheumatoid athritis

A

Disease modifying anti-rheumatics (DMARDS)

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6
Q

What adjunct therapy can be used for RA

A

Oral corticosteroid pulse

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7
Q

When are DMARDS usually prescribed

A

In newly diagnosed rheumatoid athritis

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8
Q

What drugs specifically should be prescribed if DMARDs are being given in a combination

A

Methotrexate
+ one other DMARD
+ short term glucocorticoid

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9
Q

When may combination therapy not be appropriate

A

Comorbities or pregnancies

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10
Q

What should be done if recent onset RA is being treated with combination DMARD and things seem to be ok

A

Cautiously reduce dosage

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11
Q

What drug is first choice in rheumatoid athritis

A

Methotrexate

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12
Q

How is methotrexate administered normally

A

Orally once a week on the same day
2.5mg tablets.
Dosage from 5-10mg a week

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13
Q

How should methotrexate be adminstered if oral form doesn’t work

A

Subcutaneous or IM injection

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14
Q

How many weeks pass before benefit of using methotrexate is seen

A

3-12 weeks

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15
Q

What side effects may be experienced with methotrexate (5)

A

Liver problems
Can affect blood count
Folic acid antagonist so limits DNA/ RNA synthesis
Inhibits dihydrofolate reductase and thymidylate synthethase

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16
Q

How does methotrexate enter the cell

A

Reduced folate carrier using endocytic pathway activated by a folat ereceptor

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17
Q

What happens to methotrexate once it enters the cell (5)

A
  • Polyglutamated
  • Inhibits dihydrofolate reductase
  • Conversion of dihydrofolate to tetrahydrofolate is blocked
  • Tetrahydrofolate stores depleted reducing thymidylate synthesis
  • DNA and RNA synthesis blocked
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18
Q

What is sulfasalazine

A

Antibiotic that combines sulfapyridine and salicylate with azo bond

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19
Q

How is sulfasalazine administered

A

500mg daily orally, gradually increased over 4 weeks to 1g twice a day

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20
Q

How long must you take sulfasalazine before benefit is noticed

A

12 weeks

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21
Q

What are the disadvantages of sulfasalazine

A

Not well absorbed across the gut

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22
Q

Where in sulfasalazine concentrated

A

In connective tissue and serous fluid

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23
Q

What metabolises sulfasalazine

A

Gut bacteria

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24
Q

What does sulfasalazine break down into

A

5-aminosalicylic acid

Sulfapyridine

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25
Q

Describe how sulfapyridine interacts with each part of the body

A

Absorbed rapidly in colon
Aceylated in the liver
Excreted in the urine

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26
Q

Does sulfapyridine have therapeutic action in ulcerative colitis

A

Nah

27
Q

What is the effect of 5-ASA on ulcerative colitis and how does this work

A

Induces remission

Inhibits COX, LOX PAF, cytokines, IL-1 and TNF-alpha

28
Q

What was hydroxychloroquine originally used to treat

A

Malaria

29
Q

How is hydroxychloroquine administered

A
  • oral with or after food
  • start 400mg daily
  • reduced to 2-3 times a week
30
Q

Briefly describe the mechanism of action of hydroxychloroquine

A
  • Accumulates in lysosomes increasing the pH decreasing protein modifications
  • Blocks T cell receptor 9 which recogises DNA containing immune complexes
  • Decreases dendritic cell activation
31
Q

What drug is Leflunomide’s efficacy most similar to

A

Methotrexate

32
Q

What is the dosage of Leflunomide

A

10-20mg a day

1st 3 days 100mg a day

33
Q

What is the mechanism of action of leflunomide

A

Inhibits pyrimidine biosynthesis through inhibiting dihydroorotate dehydrogenase

34
Q

How are gold salts administered

A

IM injections once a week-50mg

35
Q

How long must you be taking gold salts before a change is noticed

A

4-6 months

36
Q

How are biologicals generated

A

Genetic engineering

37
Q

What do biologicals inhibit

A
  • TNF-alpha
  • Interleukin 1
  • B cells
  • T cell stimulation
  • IL-6
  • IL-17 and 23
38
Q

Give an example of a drug that blocks TNF-alpha (2)

A

Etanercept

Infliximab

39
Q

What 2 molecules is etanercept a fusion of

A

human TNF receptor 2

Fc human IgG1

40
Q

How is etanercept administered

A

50mg once a week

Subcutaneous injection

41
Q

Describe the time scale of etanercept

A

1-4 weeks for effect

Progressive improvement 3-6 months

42
Q

What is infliximab

A

Monoclonal antibody against TNF-alpha

Antibody designed against mouse binding site of TNF-alpha with remaining 75% human IgG1

43
Q

How is infliximab administered

A

3mg/kg influsions
2-3 hours in duration
2-6 weeks apart

44
Q

Whata is adalimumab and what does it bind

A

Human TNF alpha monoclonal antibody

Binds TNF-alpha both soluble and bound

45
Q

How is adalimumab administered

A

40mg subcutaneously every other week

46
Q

Name 3 drugs that work against IL-1

A

Anakinra
Canakinumab
Rilonacept

47
Q

What is anakinra

A

Human recombinant IL-1 receptor antagonist

48
Q

Why is anakinra different from normal IL-1

A

Addition of n terminal methionine

49
Q

At what dosage is anakinra prescribed

A

100mg per day

Subcutaneous

50
Q

What is canakinumab

A

A human monoclonal antibody that target IL1B

51
Q

What is rilonacept

A

Dimeric fusion protein extracellular domain of IL1R1 and human IgG1
Used for gout

52
Q

Name a drug that works against B cells

A

Rituximab

53
Q

What is rituximab

A

Chimeric monoclonal antibody against CD20 which is primarily found on B cells

54
Q

What drug is rituximab given in combo with

A

Methotrexate

55
Q

When is rituximab presribed

A

If patients fail to respond to one or more anti-TNFa agents

56
Q

Name a drug that works against T cells

A

Abatacept

57
Q

How does abatacept work

A

Prevents second signal from being delivered to T cell

58
Q

Pros/ cons of abatacept

A

Similar clinical symptom improvement as TNFa inhib
Slower onset
Fewer adverse effects

59
Q

What does Tocilizumab act again

A

IL-6

60
Q

What drug should Tocilizumab be given in combo with

A

Methotrexate

61
Q

Name 2 drugs that can be used in psoriasis. What antibodies do they go again

A

Secukinumab for IL 17

Ustekinumab for IL 23

62
Q

what is a neutralising anti drug antibody

A

Directly interferes with biological drugs ability to work

63
Q

What is a non neutralising anti drug antibody

A

May form immune complexes around injection site reducing drug concentration and pharmacokinetics

LOCO 2 (25 decks)

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